FIGURE 11.

Motor neuron signaling and (neuro)endocrine effectors of contraction. A: motor neuronal signaling triggers excitation-contraction coupling and thereby evokes a rise in intramyocellular calcium (Ca²⁺), which enables fiber contractions, activates various signaling pathways, and modulates a transcriptional response, including retrograde feedback to the motor neuron. Motor neuron activity is modulated by sympathetic tone and includes various neurotrophic factors besides the neurotransmitter acetylcholine. B: exerkines, originating from tissues including muscle (myokines), liver (hepatokines), adipose tissue (adipokines), and bone (osteokines) as well as other hormones coordinate a systemic response to contractile activity. Many of these factors exert auto-, para-, and endocrine effects. In addition, signals can be propagated by exercise-linked changes in different metabolites (myobolites or myometabokines). β2 AR, β₂-adrenoreceptors; ATF2, activating factor 2; CaMK, calcium/calmodulin-dependent protein kinase; CnA, calcineurin A; CREB, cAMP-responsive element binding protein; ECC, excitation-contraction coupling; GDF3, growth differentiation factor 3; IGF-1, insulin-like growth factor 1; IL-13, interleukin 13; NTs, neurotrophic factors; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1α; symp. NS, sympathetic nervous system; TF, transcription factor. Image created with BioRender.com, with permission.